Maintenance, development, regeneration and neuronal death are common processes of our nervous central system that can be found altered in Alzheimer’s disease (AD), and are controlled or influenced by specific genes. In order to verify putative associations of some of these genes and AD, we have screened databases of Expressed Sequence Tags (ESTs) for the identification of putative Single Nucleotide Polymorphisms (SNPs). The set of sequences evaluated consisted of almost 5 million sequences, including 1.2 million ESTs derived from the central coding regions of human genes (ORESTES), produced by our group. Particular attention was given to putative SNPs that would be translated into aminoacid alterations in the coded protein. A polymorphism selected was identified in brain-derived neurotrophic factor (BDNF) gene. Several lines of evidence makes the BDNF gene an important candidate gene for AD. The alteration we found is a G>A substitution that is translated in a VAL66MET alteration in the protein. It was recently showed that this polymorphism in BDNF protein affects human memory and hippocampal function, which are impaired in AD patients. In our study, this polymorphism was investigated by direct DNA sequencing in a Brazilian sample of 189 AD patients as well as in 140 cognitively healthy controls (matched by age and sex). While allelic and genotipic frequencies were similar among cases and controls, statistical significance was consistently observed between early and late onset disease patients (P=0.047; O.R.=2.54, C.I.=1.01-6.41). The results shows the potential of this analysis for a better understanding of complex diseases such as AD.
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